FDA Grants Fast Track Designation to BXCL701 for Small Cell Neuroendocrine Prostate Cancer


BXCL701 has been granted fast track designation for select patients with metastatic small cell neuroendocrine prostate cancer by the FDA.



The FDA has granted fast track designation to the oral innate immune activator BXCL701 in combination with an immune checkpoint inhibitor for the treatment of patients with metastatic small cell neuroendocrine prostate cancer with progression on chemotherapy and no evidence of microsatellite instability.1

The agent is currently under evaluation in combination with pembrolizumab (Keytruda) in a phase 2 trial (NCT03910660) of patients with metastatic castration-resistant prostate cancer (mCRPC) with small cell neuroendocrine carcinoma (SCNC) and adenocarcinoma phenotypes. In the SCNC cohort (n = 28), the median overall survival (OS) was 13.6 months (95% CI, 10.9-not reached [NR]), and the 12-month OS rate was 56.5%.2

In the adenocarcinoma cohort, at the most recent data cutoff of September 6, 2023, the combination led to a median OS of 15.5 months (95% CI, 9.6-NR), with a 12-month OS rate of 59% in 29 evaluable patients.3

“The FDA’s fast track designation for the investigation of BXCL701 in SCNC is an important recognition of our most advanced immuno-oncology asset and an acknowledgment of its potential to address the considerable unmet medical need in these patients. At the same time, it further validates the unique AI-based drug re-innovation approach that we used to discover this asset,” Vimal Mehta, PhD, chief executive officer of BioXcel Therapeutics, said in a news release.1 “BXCL701 has already demonstrated considerable potential in our clinical trials to date, and we plan to further define its development path while exploring strategic options for our OnkosXcel Therapeutics subsidiary.”

The open-label, single-arm, multicenter phase 2 trial is evaluating the safety and efficacy of the combination in patients with mCRPC of the adenocarcinoma or SCNC phenotype.2 To be eligible for enrollment patients must have evidence of progressive mCRPC, as defined by Prostate Cancer Working Group 3 criteria, with documented progression during or following completion of at least 1 prior line of systemic therapy for locally advanced or metastatic disease.4 Prior androgen deprivation therapy was not required for patients with de novo small cell prostate cancer. Additional eligibility criteria required serum testosterone levels below 50 ng/dL during screening except for those with de novo small cell prostate cancer.

In the SCNC cohort BXCL701 was administered twice daily at a dose of 0.2 mg on days 1 through 7, 0.3 mg on days 7 through 14 for the first 21-day cycle and 0.3 mg thereafter; 200 mg of intravenous pembrolizumab was administered alongside BXCL701 on day 1 of each cycle.2

The primary end point of the trial is the composite response rate quantified by objective response per RECIST v1.1 criteria and/or prostate specific antigen reduction of at least 50% (PSA50) and/or circulating tumor count (CTC) conversion. Secondary end points include duration of response (DOR), progression-free survival, OS, and biomarker assessment as determined by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.2

Findings from the phase 2a portion of the trial, which were presented at the 2023 Genitourinary Cancers Symposium, indicated that the composite response rate was 25% (95% CI, 8.3%-41%) in the SCNC population.5 In evaluable patients (n = 25), the overall response rate was 20% (95% CI, 6.8%-40.7%) per RECIST v1.1 criteria.

Additional findings showed that the composite DOR with the combination was 6+ months (range, 1.3-17.4), and the median DOR was 6+ months (range, 1.8-9.8) per RECIST v1.1 criteria. Among patients evaluable for PSA (n = 27), 11% (95% CI, 2.4%-29%) had PSA50 from baseline. Additionally, 1 of the 4 patients evaluable for CTCs had a CTC response rate (95% CI, 0.6%-80.6%).

Regarding safety, the most frequent treatment-related adverse effects (AEs) included fatigue (32%), hypotension (21%), pruritus (21%), dizziness (18%), and nausea (12%). Any-grade immune-related AEs were experienced by 41% of patients, including 7% who reported grade 3 or higher events.

In terms of tolerability, 18% of patients discontinued treatment because of an AE; 18% of cases were deemed related d to BXCL701 and 15% were associated with pembrolizumab.

“SCNC is characterized by poor prognosis and a low survival rate, and current treatment options are suboptimal,” Vincent J. O’Neill, MD, executive vice president and chief of Product Development and Medical Officer of BioXcel Therapeutics, said in the news release.1 “We are encouraged by the potential of BXCL701, which has demonstrated clinical proof of concept in both SCNC and adenocarcinoma. Following the positive survival results from our phase 2 trial that we reported at the end of last year, we look forward to further discussing the registration path at an upcoming meeting with the FDA.”

Of note, BXCL701 tablets are formulated with dosage strengths of 0.05 mg and 1 mg and should not be taken on an empty stomach.4


  1. BioXcel Therapeutics receives FDA fast track designation for BXCL701 for treatment of small cell neuroendocrine prostate cancer (SCNC). News release. BioXcel Therapeutics. February 12, 2024. Accessed February 12, 2024. https://www.biospace.com/article/releases/bioxcel-therapeutics-receives-fda-fast-track-designation-for-bxcl701-for-treatment-of-small-cell-neuroendocrine-prostate-cancer-scnc-/?keywords=cancer
  2. BioXcel Therapeutics reports positive overall survival results from single-arm, open-label phase 2 trial of BXCL701 in patients with small cell neuroendocrine prostate cancer. News release. BioXcel Therapeutics. October 10, 2023. Accessed February 12, 2024. https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results
  3. BioXcel Therapeutics reports positive overall survival results from single-arm, open-label phase 2 trial of BXCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype. BioXcel Therapeutics, Inc. News release. November 8, 2023. Accessed February 12, 2024. https://www.globenewswire.com/news-release/2023/11/08/2776064/0/en/BioXcel-Therapeutics-Reports-Positive-Overall-Survival-Results-from-Single-Arm-Open-Label-Phase-2-Trial-of-BXCL701-in-Patients-with-Metastatic-Castration-Resistant-Prostate-Cancer-.html
  4. A trial of BXCL701 and pembrolizumab in patients with mCRPC either small cell neuroendocrine prostate cancer or adenocarcinoma phenotype. ClinicalTrials.gov. Updated May 23, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03910660
  5. Aggarwal RR, Zhang J, Monk P, et al. First-in-class oral innate immune activator BXCL701 codmbined with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) phenotype: Phase 2a final results. J Clin Oncol. 2023;41(suppl 6):176. doi:10.1200/JCO.2023.41.6_suppl.176
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